ABSTRACT The long-term goal of our research is to determine if exposure to contaminants from the World Trade Center (WTC) disaster of September 11, 2001 caused neuropathic symptoms, and nervous system injuries in the WTC ?Survivor? population. Our preliminary findings demonstrate a high prevalence of neurologic symptoms among both Survivors from the general community and first responders. There are numerous causes of neuropathic symptoms, however, such as diabetes, anemia, anxiety, and exposure to non-WTC-related neurotoxins. Neuropathic symptoms thus need to be investigated to understand whether they are due to WTC exposures. The first objective of this project is to explore the connection between WTC exposure and neuropathic symptoms through use of existing longitudinal data and neurological studies. Our second objective is to refine our understanding of neurologic symptoms with more complete questionnaires, neurological examination and objective testing (electromyography/nerve conduction velocity [EMG/NCV]; histopathologic evaluations; and blood tests for HgbA1c, B12, exposure to neurotoxic infectious agents, and neuron-specific enolase) in the context of a case-control study of patients with and without neuropathic symptoms. Our specific aims are (1) to analyze longitudinal data to describe the evolution of paresthesias in the survivor population; and (2) to analyze EMG/NCV data in order to investigate the pathophysiology of the reported paresthesias; and (3) to examine whether neuropathic symptoms among Survivors and Responders are associated with abnormalities in nerve fiber densities or EMG/nerve conduction studies. Already- performed EMG/NCV studies neurologic studies (n=80) will be analyzed to determine their relationship to neuropathic symptoms and to explore correlates of persistence, deterioration or improvement over time in these symptoms. We will evaluate nerve fiber densities as risk factors for neuropathic symptoms as part of the case-control study. Cases will be 40 patients with persistent neuropathic symptoms on at least 2 study visits drawn from patients enrolled in the Bellevue WTC Environmental Health Center (WTC EHC). Controls (n=40) will be drawn from the same WTC EHC population; individually matched to cases on age, race, gender and absence of histories of diabetes, cancer and paresthesias or neurologic disorders prior to 9/11/2001; but free of paresthesias on all study visits. A community-based, non-WTC-exposed control group (n=20) also will be enrolled, frequency-matched to cases on the same matching variables as the WTC EHC controls, in order to determine the prevalence of abnormalities in the general population without WTC-exposure. Case-control study participants found to have neuropathic symptoms will be referred for optional EMG/NCV studies to elucidate mechanisms underlying neuropathic symptoms. Successful completion of this project will clarify whether exposure to WTC toxins caused the observed neuropathic symptoms.